Description: Das Projekt "Molekularbiologische Untersuchungen zum XRCC1-Gen" wird vom Umweltbundesamt gefördert und von Universität Bonn, Institut für Experimentelle Radiologie und Strahlenbiologie durchgeführt. We investigated cell inactivation and mutation induction at the hprt locus in cultured V79 Chinese Hamster Cells irradiated with four different accelerated heavy ions (O, Ca, Au, U). Specific energies ranged from 1.9 to 69.7 MeV/u and corresponding LET-values were between 62 and 15,580 keV/mikrometre. 30 spontaneous and 196 heavy ion-induced 6-thioguanine-resistant hprt mutant clones were characterized by Southern-technique using three restriction enzymes (Eco RI, Pst I, Bgl II) and a full-length hprt cDNA isolated from the plasmid pHpt12 (kindly provided by Dr. J. Thacker). While inactivation cross sections (si) seem to rise over the whole LET-range, mutation induction cross sections (sm) increase up to approximately 300 keV/mikrometre (O-ions) but decfine with heavier ions and more extreme LET-values. A similar behaviour is seen with mutation frequency in dependence on particle fluence. After irradiation with accelerated uranium ions (8,8 MeV/u, 15580 keV/mikrometre) we found a significant decrease of mutation frequency with higher particle fluences ( 3.106 particles/cm2). Nearly no mutants were recovered with 8.106 particles/cm2. All restriction patterns of the spontaneous hprt mutants were indistinguishable from the wild type. These mutants probably containsmall deletions or point mutations in the hprt locus. In contrast, the overall spectrum of heavy ion-induced mutations revealed a majority (67 per cent) of deletions of all or part of the hprt gene. With constant particle fluence (3.106 particles/cm2) the quality of heavy ion-induced mutations in the hprt locus depends on physical beam parameters (atomic number, specific energy, LET). This finding suggests a relationship between the type of DNA damage and track structure. The fraction of mutants with severe deletions in the hprt locus increases with LET from 65 per cent at 60 keV/mikrometre up to a maximum (100 per cent) at 300 keV/mikrometre and declines with higher LET-values to 75 per cent at 750 keV/mikrometre (O-ions). With heavier ions (Au and U) and even higher LET-values this mutant fraction decreases further to 58 per cent at 13,200 keV/mikrometre. Heavy ion-induced DNA break points in the hprt locus are not randomly distributed. 71 per cent of the break points are located near the center of the gene (in the vicinity of exon 5).
Types:
SupportProgram
Origin: /Bund/UBA/UFORDAT
Tags: Bonn ? Gen ? Hamster ? Mutation ? Strahlenbiologie ? Seen ? DNA ? Genetik ? Uran ? Biochemische Untersuchung ? Enzym ? Kernenergie ? Energie ? Ionen ? Kenngröße ? Partikel ? Komplementäre DNA ? Plasmid ?
Region: Nordrhein-Westfalen
Bounding box: 6.76339° .. 6.76339° x 51.21895° .. 51.21895°
License: cc-by-nc-nd/4.0
Language: Deutsch
Time ranges: 1996-05-01 - 1998-05-31
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